Metabolic syndrome (or Syndrome X) is characterized by a group of metabolic risk factors in one person that include, for example, central obesity (i.e., excessive fat tissue in and around the abdomen), atherogenic dyslipidemia (i.e., blood fat disorders—mainly high triglycerides and low HDL cholesterol—that foster plaque buildups in artery walls), raised blood pressure (e.g., 130/85 mmHg or higher), insulin resistance or glucose intolerance (the body can't properly use insulin or blood sugar), prothrombotic state (e.g., high fibrinogen or plasminogen activator inhibitor in the blood), and pro inflammatory state (e.g., elevated high-30 sensitivity C-reactive protein in the blood).
The underlying causes of this syndrome are overweight/obesity, physical inactivity and genetic factors. People with the metabolic syndrome are at increased risk of coronary heart disease, other diseases related to plaque buildups in artery walls (e.g., stroke and 35 peripheral vascular disease) and type 2 diabetes.
Metabolic syndrome has become increasingly common in the United States. It's estimated that about 47 million U.S. adults have it. The syndrome is closely associated with a generalized metabolic disorder called insulin resistance, in which the body cannot use insulin efficiently. This is why the metabolic syndrome is also called the insulin resistance syndrome. Some people are genetically predisposed to insulin resistance. Acquired factors, such as excess body fat and physical inactivity, can elicit insulin resistance and the metabolic syndrome in these people. Most people with insulin resistance have central obesity. The biologic mechanisms at the molecular level between insulin resistance and metabolic risk factors are not fully understood and appear to be complex.
Conventional treatment typically includes dietary changes to limit fat and calories, increased exercise, and changes in habits or patterns of eating. Medications commonly prescribed for weight loss include numerous metabolic stimulants, perhaps in combination with cholesterol lowering drugs and/or high blood pressure medications. However, such compounds may not be effective in all subjects, or may be of limited efficacy. Accordingly, new treatments for metabolic syndrome and its associated factors are needed.
Caloric restriction is known to extend lifespan in mammals. Caloric restriction also reduces the incidence of age-associated conditions such as obesity, insulin resistance, dyslipidemia, and cancer. Resveratrol, a polyphenol derived from red wine, is a “phytoestrogen” that mimics caloric restriction by activating Sir2 and extending lifespan in several species. Resveratrol is also known to have anti-inflammatory and anti-angiogenic effects, as well as preventive effects to atherosclerosis.
Resveratrol has been shown to reduce fat accumulation in C. elegans and in several insulin-sensitive mammalian cell lines Inhibition of AMP-activated kinase gene expression is also known to prevent the effect of reseveratrol on fat accumulation. Accordingly, the effect of resveratrol on fat accumulation depends on Sir2.1. Thus, resveratrol-like compounds will prove useful in the prevention and treatment of diseases and risk factors associated with metabolic syndrome.
Consequently, it would be desirable to provide resveratrol analogs, resveratrol-like compounds, and polymers thereof, as well as methods of using such compounds in preventing and treating diseases and risk factors associated with metabolic syndrome.